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Clinicopathological and prognostic significance of H3K27 methylation status in malignant peripheral nerve sheath tumor: correlation with skeletal muscle differentiation
Virchows Archiv ( IF 3.4 ) Pub Date : 2021-08-25 , DOI: 10.1007/s00428-021-03189-0
Yoshihiro Ito 1, 2 , Kenichi Kohashi 1 , Makoto Endo 2 , Masato Yoshimoto 2, 3 , Shin Ishihara 1, 2 , Yu Toda 1 , Yosuke Susuki 1, 2 , Kengo Kawaguchi 1, 2 , Hiroshi Furukawa 1, 2 , Yuki Tateishi 1 , Yuichi Yamada 1 , Izumi Kinoshita 1 , Taro Mori 1 , Hidetaka Yamamoto 1 , Yasuharu Nakashima 2 , Yoshinao Oda 1
Affiliation  

Malignant peripheral nerve sheath tumor (MPNST) is a very aggressive peripheral nerve sheath-derived sarcoma, which is one of the most difficult tumors to diagnose due to its wide spectrum of histological findings and lack of specific immunohistochemical markers. Recently, it has been reported that losses of expression of H3K27me3 and H3K27me2 caused by PRC2 dysfunction may be useful diagnostic markers for MPNST, but there is no consensus on their clinicopathological significance. Here, we investigated the relationship between loss of H3K27 methylation and various parameters and clarified the clinicopathological significance of such loss. We analyzed the clinicopathological and immunohistochemical features in 84 MPNST cases. Complete losses of H3K27me3 and H3K27me2 were observed in 37 (44%) and 29 (35%) cases, respectively. Losses of H3K27me3 and H3K27me2 were significantly correlated with myogenic immunopositivity (H3K27me3 vs. desmin, P = 0.0051; H3K27me3 vs. myogenin, P = 0.0009; H3K27me2 vs. myogenin, P = 0.042). Meanwhile, there were significant correlations between preservation of immunohistochemical neurogenic markers and intact H3K27me3 and H3K27me2 (H3K27me3 vs. S-100 protein, P = 0.0019; H3K27me3 vs. SOX10, P = 0.014; H3K27me2 vs. S-100 protein, P = 0.0011; H3K27me2 vs. SOX10, P = 0.0087). In multivariate analysis, local recurrence, distant metastasis, high FNCLCC grade, and loss of SOX10 expression were independent prognostic factors for overall survival. H3K27me3 and H3K27me2 expression was retained in all 26 cases of rhabdomyosarcoma non-alveolar subtype. In conclusion, we suggest that H3K27me3 and H3K27me2 immunonegativity is useful but not definitive for diagnosing MPNST. Complete loss of H3K27 methylation may be involved in aggressive transdifferentiation from neural differentiation to skeletal muscle differentiation in MPNST.



中文翻译:

H3K27甲基化状态在恶性周围神经鞘瘤中的临床病理学和预后意义:与骨骼肌分化的相关性

恶性外周神经鞘瘤(MPNST)是一种非常侵袭性的外周神经鞘源性肉瘤,由于其广泛的组织学发现和缺乏特异性免疫组织化学标志物,是最难诊断的肿瘤之一。最近有报道称,PRC2 功能障碍引起的 H3K27me3 和 H3K27me2 表达缺失可能是 MPNST 的有用诊断标志物,但其临床病理学意义尚未达成共识。在这里,我们研究了 H3K27 甲基化缺失与各种参数之间的关系,并阐明了这种缺失的临床病理学意义。我们分析了 84 例 MPNST 病例的临床病理学和免疫组化特征。分别在 37 (44%) 和 29 (35%) 例中观察到 H3K27me3 和 H3K27me2 完全丢失。P  = 0.0051;H3K27me3 与肌细胞生成素,P  = 0.0009;H3K27me2 与肌细胞生成素,P  = 0.042)。同时,免疫组化神经源性标志物的保存与完整的 H3K27me3 和 H3K27me2 之间存在显着相关性(H3K27me3 vs. S-100 蛋白,P  = 0.0019;H3K27me3 vs. SOX10,P  = 0.014;H3K27me2 vs. S-100 蛋白,P  = 0.0011 ; H3K27me2 与 SOX10,P = 0.0087)。在多变量分析中,局部复发、远处转移、高 FNCLCC 分级和 SOX10 表达缺失是总生存期的独立预后因素。H3K27me3 和 H3K27me2 表达在所有 26 例横纹肌肉瘤非肺泡亚型中均保留。总之,我们建议 H3K27me3 和 H3K27me2 免疫阴性对于诊断 MPNST 是有用的,但不是明确的。H3K27 甲基化的完全丧失可能与 MPNST 中从神经分化到骨骼肌分化的侵袭性转分化有关。

更新日期:2021-08-25
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